Introduction

The invention concerns two new peptides and related pharmaceutical compositions for the treatment of diseases and pathological conditions associated with impaired motility, migration and cell adhesion such as angiogenesis, invasion and tumor metastases. In particular, the authors propose two decapeptides (linear and its cyclic form) capable of inhibiting cell migration, preventing the formation of tumor metastases.

Technical features

Metastatic dissemination of cancer cells is the major cause of mortality in advanced cancers. Solid tumors are initially small cellular aggregates in which cells, with the progression of malignancy, acquire the ability to move, migrate, and destroy the tissue barriers that physiologically contrast them. In addition, the non-tumor tissue cells surrounding the tumor, in particular the Cancer-Associated Fibroblasts or CAF are also induced over time to produce factors that support tumor growth and dissemination. The inventors have identified peptides capable of both directly inhibiting the migration of neoplastic cells and blocking the pro-invasive effect of the surrounding non-tumor cells. The target of the peptides is the avb5 integrin receptor: the new compounds block the functioning of this integrin, which is involved in the regulation of tumor cell adhesion and movement. These novel peptides inhibit the pulmonary metastases of fibrosarcoma cells in mice and counteract the support of cancer-associated fibroblasts or CAFs surrounding solid neoplasms. Therefore, they can be regarded as lead compounds for the development of new anti-neoplastic therapies with co-targeting strategies.

Possible Applications

• Antitumor therapies to counteract the migratory and invasive capacity of neoplastic cells;
• Antitumor therapies to counteract the “support” of the CAF peritumoral fibroblasts;
• Treatment of pathologies associated with an excess of cellular migration such as neoplastic, ocular and chronic inflammations.

Advantages

• Stable and effective inhibition of tumor migration and invasion at nanomolar concentrations;
• Efficacy both on the tumor component (fibrosarcomas and breast carcinomas) and on the tumor microenvironment Cancer-Associated Fibroblasts (CAF);
• A 75% reduction in the number and size of lung metastases was observed in mouse models;
• No toxic effects observed in in vivo experiments;
• Reduction of therapy costs and side effects.